Characterizing the phenotypic manifestations of MFN2 R104W mutation in Charcot-Marie-Tooth type 2

Neuromuscul Disord. 2011 Jun;21(6):428-32. doi: 10.1016/j.nmd.2011.03.008. Epub 2011 Apr 29.


Mutations of the mitofusin 2 (MFN2) gene have been reported to be the most common cause of the axonal form of Charcot-Marie-Tooth disease (CMT). The aim of this study was to describe a de novo MFN2 p.R104W mutation and characterize the associated phenotype. We screened the entire coding region of MFN2 gene and characterized its clinical phenotype, nerve conduction studies and sural nerve biopsy. Neuropsychological tests and brain MRI were also performed. A de novo mutation was found in exon 4 (c.310C>T; p.R104W). In addition to a severe and early onset axonal neuropathy, the patient presented learning problems, obesity, glucose intolerance, leukoencephalopathy, brain atrophy and evidence of myelin involvement and mitochondrial structural changes on sural nerve biopsy. These results suggest that MFN2 p.R104W mutation is as a hot-spot for MFN2 gene associated to a large and complex range of phenotypes.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biopsy
  • Brain / pathology
  • Charcot-Marie-Tooth Disease / genetics*
  • Charcot-Marie-Tooth Disease / pathology*
  • Charcot-Marie-Tooth Disease / physiopathology
  • GTP Phosphohydrolases
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Membrane Proteins / genetics*
  • Mitochondrial Proteins / genetics*
  • Mutation / genetics*
  • Neural Conduction / physiology
  • Neuropsychological Tests
  • Phenotype*
  • Sural Nerve / pathology


  • Membrane Proteins
  • Mitochondrial Proteins
  • GTP Phosphohydrolases
  • MFN2 protein, human